USP13 controls the stability of Aurora B impacting progression through the cell cycle

Mara Esposito, H Begum Akman, Philippe Giron, M Angeles Ceregido, Rogier Schepers, Luis C Ramos Paez, Esther La Monaca, Jacques De Greve, Olivier Coux, Carl De Trez, Catherine Lindon, Gustavo J Gutierrez

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Aurora B kinase plays essential roles in mitosis. Its protein levels increase before the onset of mitosis and sharply decrease during mitosis exit. The latter decrease is due to a balance between the actions of the E3 ubiquitin ligase anaphase-promoting complex or cyclosome (activated by the Cdh1 adapter), and the deubiquitinating enzyme USP35. Aurora B also executes important functions in interphase. Abnormal modulation of Aurora B in interphase leads to cell cycle defects often linked to aberrant chromosomal condensation and segregation. Very little is however known about how Aurora B levels are regulated in interphase. Here we found that USP13-associates with and stabilizes Aurora B in cells, especially before their entry into mitosis. In order for USP13 to exert its stabilizing effect on Aurora B, their association is promoted by the Aurora B-mediated phosphorylation of USP13 at Serine 114. We also present evidence that USP13 instigates Aurora B deubiquitination and/or protect it from degradation in a non-catalytic manner. In addition, we report that genetic or chemical modulation of the cellular levels/activity of USP13 affects unperturbed cell-cycle progression. Overall our study unveils the molecular and cellular connections of the USP13-Aurora B axis, which potentially participates in the rewiring of the cell cycle happening in cancer cells.

Original languageEnglish
Pages (from-to)6009-6023
Number of pages15
JournalOncogene
Volume39
Issue number37
DOIs
Publication statusPublished - Sep 2020

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